Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma
Abstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (T...
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2018-08-01
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doaj-23bb514e9fc84cb880e52835f19ae0f82020-12-08T03:46:01ZengNature Publishing GroupScientific Reports2045-23222018-08-018111110.1038/s41598-018-31126-wTargeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinomaLucas A. Tomko0Ryan C. Hill1Alexander Barrett2Joseph M. Szulczewski3Matthew W. Conklin4Kevin W. Eliceiri5Patricia J. Keely6Kirk C. Hansen7Suzanne M. Ponik8Department of Cell and Regenerative Biology, University of Wisconsin-MadisonDepartment of Biochemistry and Molecular Genetics, University of Colorado-DenverDepartment of Biochemistry and Molecular Genetics, University of Colorado-DenverDepartment of Cell and Regenerative Biology, University of Wisconsin-MadisonDepartment of Cell and Regenerative Biology, University of Wisconsin-MadisonLaboratory for Optical and Computational Instrumentation, University of Wisconsin at MadisonDepartment of Cell and Regenerative Biology, University of Wisconsin-MadisonDepartment of Biochemistry and Molecular Genetics, University of Colorado-DenverDepartment of Cell and Regenerative Biology, University of Wisconsin-MadisonAbstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (TACS). Late stages of this progression are characterized by the presence of bundled, straight collagen (TACS-2) that become oriented perpendicular to the tumor-stromal boundary (TACS-3). Importantly, the presence of TACS-3 collagen is an independent predictor of poor patient outcome. At present, it remains unclear whether reorganization of the collagen matrix is the consequence of mechanical or compositional tissue remodeling. Here, we identify compositional changes in ECM correlating to collagen fiber reorganization from nineteen normal and invasive ductal carcinoma (IDC) patient biopsies using matrisome-targeted proteomics. Twenty-seven ECM proteins were significantly altered in IDC samples compared to normal tissue. Further, a set of nineteen matrisome proteins positively correlate and five proteins inversely correlate with IDC tissues containing straightened collagen fibers. Tenascin-C and thrombospondin-2 significantly co-localized with aligned collagen fibers in IDC tissues. This study highlights the compositional change in matrisome proteins accompanying collagen re-organization during breast cancer progression and provides candidate proteins for investigation into cellular and structural influences on collagen alignment.https://doi.org/10.1038/s41598-018-31126-w |
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DOAJ |
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English |
format |
Article |
sources |
DOAJ |
author |
Lucas A. Tomko Ryan C. Hill Alexander Barrett Joseph M. Szulczewski Matthew W. Conklin Kevin W. Eliceiri Patricia J. Keely Kirk C. Hansen Suzanne M. Ponik |
spellingShingle |
Lucas A. Tomko Ryan C. Hill Alexander Barrett Joseph M. Szulczewski Matthew W. Conklin Kevin W. Eliceiri Patricia J. Keely Kirk C. Hansen Suzanne M. Ponik Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma Scientific Reports |
author_facet |
Lucas A. Tomko Ryan C. Hill Alexander Barrett Joseph M. Szulczewski Matthew W. Conklin Kevin W. Eliceiri Patricia J. Keely Kirk C. Hansen Suzanne M. Ponik |
author_sort |
Lucas A. Tomko |
title |
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma |
title_short |
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma |
title_full |
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma |
title_fullStr |
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma |
title_full_unstemmed |
Targeted matrisome analysis identifies thrombospondin-2 and tenascin-C in aligned collagen stroma from invasive breast carcinoma |
title_sort |
targeted matrisome analysis identifies thrombospondin-2 and tenascin-c in aligned collagen stroma from invasive breast carcinoma |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2018-08-01 |
description |
Abstract Increasing evidence demonstrates an important role for the extracellular matrix (ECM) in breast cancer progression. Collagen type I, a core constituent of the fibrous ECM, undergoes a significant set of changes that accompany tumor progression, termed Tumor Associated Collagen Signatures (TACS). Late stages of this progression are characterized by the presence of bundled, straight collagen (TACS-2) that become oriented perpendicular to the tumor-stromal boundary (TACS-3). Importantly, the presence of TACS-3 collagen is an independent predictor of poor patient outcome. At present, it remains unclear whether reorganization of the collagen matrix is the consequence of mechanical or compositional tissue remodeling. Here, we identify compositional changes in ECM correlating to collagen fiber reorganization from nineteen normal and invasive ductal carcinoma (IDC) patient biopsies using matrisome-targeted proteomics. Twenty-seven ECM proteins were significantly altered in IDC samples compared to normal tissue. Further, a set of nineteen matrisome proteins positively correlate and five proteins inversely correlate with IDC tissues containing straightened collagen fibers. Tenascin-C and thrombospondin-2 significantly co-localized with aligned collagen fibers in IDC tissues. This study highlights the compositional change in matrisome proteins accompanying collagen re-organization during breast cancer progression and provides candidate proteins for investigation into cellular and structural influences on collagen alignment. |
url |
https://doi.org/10.1038/s41598-018-31126-w |
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